Emergence of macroscopic directed motion in populations of motile colloids

From the formation of animal flocks to the emergence of coordinate motion in bacterial swarms, at all scales populations of motile organisms display coherent collective motion. This consistent behavior strongly contrasts with the difference in communication abilities between the individuals. Guided by this universal feature, physicists have proposed that solely alignment rules at the individual level could account for the emergence of unidirectional motion at the group level. This hypothesis has been supported by agent-based simulations. However, more complex collective behaviors have been systematically found in experiments including the formation of vortices, fluctuating swarms, clustering and swirling. All these model systems predominantly rely on actual collisions to display collective motion. As a result, the potential local alignment rules are entangled with more complex, often unknown, interactions. The large-scale behavior of the populations therefore depends on these uncontrolled microscopic couplings. Here, we demonstrate a new phase of active matter. We reveal that dilute populations of millions of colloidal rollers self-organize to achieve coherent motion along a unique direction, with very few density and velocity fluctuations. Identifying the microscopic interactions between the rollers allows a theoretical description of this polar-liquid state. Comparison of the theory with experiment suggests that hydrodynamic interactions promote the emergence of collective motion either in the form of a single macroscopic flock at low densities, or in that of a homogenous polar phase at higher densities. Furthermore, hydrodynamics protects the polar-liquid state from the giant density fluctuations. Our experiments demonstrate that genuine physical interactions at the individual level are sufficient to set homogeneous active populations into stable directed motion

Collective beating of artificial microcilia

We combine technical, experimental and theoretical efforts to investigate the collective dynamics of artificial microcilia in a viscous fluid. We take advantage of soft-lithography and colloidal self-assembly to devise microcapets made of hundreds of slender magnetic rods. This novel experimental setup is used to investigate the dynamics of extended cilia arrays driven by a precessing magnetic field. Whereas the dynamics of an isolated cilium is a rigid body rotation, collective beating results in a symmetry breaking of the precession patterns. The trajectories of the cilia are anisotropic and experience a significant structural evolution as the actuation frequency increases. We present a minimal model to account for our experimental findings and demonstrate how the global geometry of the array imposes the shape of the trajectories via long range hydrodynamic interactions.Comment: 5 pages, 3 figure

Emergent vortices in populations of colloidal rollers

Coherent vortical motion has been reported in a wide variety of populations including living organisms (bacteria, fishes, human crowds) and synthetic active matter (shaken grains, mixtures of biopolymers), yet a unified description of the formation and structure of this pattern remains lacking. Here we report the self-organization of motile colloids into a macroscopic steadily rotating vortex. Combining physical experiments and numerical simulations, we elucidate this collective behavior. We demonstrate that the emergent-vortex structure lives on the verge of a phase separation, and single out the very constituents responsible for this state of polar active matter. Building on this observation, we establish a continuum theory and lay out a strong foundation for the description of vortical collective motion in a broad class of motile populations constrained by geometrical boundaries

Quality control of antibiotics before the implementation of an STD program in Northern Myanmar.

BACKGROUND: The ready availability of poor-quality drugs in developing countries leads to treatment failure and, consequently, excess mortality and morbidity. Moreover, the widespread availability of substandard drugs plays a key role in increasing the resistance to antimicrobial drugs.GOAL As a prerequisite to the establishment of a sexually transmitted disease (STD) control program, this study aimed to evaluate the quality of antibiotics recommended for treatment of STDs that were locally available in the capital of a province of Northern Myanmar. STUDY DESIGN: In addition to the hospital pharmacy, we selected at random 5 of the 41 drug sellers and 5 of the 40 general practitioners who sell antibiotics in the city of Myitkyina. Twenty-one marketing products corresponding to nine different antibiotics used for STD treatment were purchased (benzathine benzylpenicillin, benzylpenicillin, ceftriaxone, chlortetracycline, ciprofloxacin, clotrimazole, co-trimoxazole, doxycycline, and erythromycin). Drugs were sent to France, where they were analyzed according to the WHO guidelines. Drugs were considered to be standard if their dosage remained in the 10% range of the expected value. RESULTS: Among the 21 different specialty products, only three displayed the official "registered" label. Three drugs were expired and the expiration date was not available for six others. One product did not contain the active drug declared (chlortetracycline; Lombisin, Unicorn, China) and did not show any in vitro activity against bacteria. Seven of 21 products (33%) did not contain the stated dosage (1, more than stated dosage; 6, less than stated dosage). The highest deficit observed was 48% in two products (co-trimoxazole, Yong Fong, Myanmar; benzylpenicillin, China [city and manufacturer unknown]). The dosage was not available for five drugs. As a result, only 8 of 21 products (38%) did not contain the stated dosage of active drug. CONCLUSION: These findings suggest that public health policies based on national treatment guidelines should rigorously include the monitoring of quality control of available antimicrobial products. In the absence of such measures, specific treatment strategies are likely to fail and to generate drug resistance

Downregulation of basophil-derived IL-4 and in vivo TH2 IgE responses by serotonin and other organic cation transporter 3 ligands

International audienceBACKGROUND:Murine basophils can contribute to the T(H)2 polarization of the immune response by providing rapidly large amounts of IL-4, which suggests that pharmacologic downregulation of this cytokine might provide a strategy to attenuate pathologies associated with excessive production.OBJECTIVE:We examined a number of physiological and pharmacologic ligands of the organic cation transporter 3 (OCT3), a membrane carrier of biogenic amines, for their inhibitory effect on IL-4 production by basophils, selecting the most efficient compounds for in vivo evaluation in basophil-dependent experimental models.METHODS:IL-4 production by basophils isolated ex vivo or from bone marrow cultures was assessed in response to various stimuli with or without biogenic monoamines or pharmacologic analogs. Selected compounds were administered in vivo to examine their effect on levels of circulating IgE generated during a basophil-dependent T(H)2 response and on basophil activation in mice receiving IL-33.RESULTS:We found a drastic decrease in IL-4 production by stimulated basophils on exposure to serotonin (5-hydroxytryptamine [5-HT]) that is taken up by basophils through the specific high-affinity transporters serotonin transporter and the polyspecific, high-capacity organic cation transporter 3 (OCT3; or Slc22a3) but inhibits their function exclusively through the latter. This downregulation is likewise observed in vivo in response to 5-HT and other OCT3 ligands, as well as in human basophils sorted from PMBCs of nonatopic donors.CONCLUSIONS:We provide evidence for a new means of downregulating IL-4 production by basophils, both in vitro and in vivo, through OCT3 targeted by 5-HT and pharmacologic ligands

Successful treatment of JAK1 associated inflammatory disease

International audienceBackground: Gain of function (GOF) variants of JAK1 drive a rare immune dysregulation syndrome associated with atopic dermatitis, allergy and eosinophilia.Objectives: To describe the clinical and immunological characteristics associated with a new GOF variant of JAK1 and report the therapeutic efficacy of JAK inhibition.Methods: We identified a family affected by JAK1 associated autoinflammatory disease and performed clinical assessment and immunological monitoring on 9 patients. JAK1 signalling was studied by flow and mass cytometry in patients' cells at basal state, or after immune stimulation. A molecular disease signature in the blood was studied at the transcriptomic level. Patients were treated with one of two JAK inhibitors; either baricitinib or upadacitinib. Clinical, cellular, and molecular response were evaluated over a 2-year period.Results: Affected individuals displayed a syndromic disease with prominent allergy including atopic dermatitis, ichthyosis, arthralgia, chronic diarrhoea, disseminated calcifying fibrous tumours and elevated whole blood histamine levels. A variant of JAK1 localized in the pseudokinase domain was identified in all 9 affected tested patients. Hyper-phosphorylation of STAT3 was found in 5 out of 6 patients tested. Treatment of patients' cells with baricitinib controlled most of the atypical hyper-phosphorylation of STAT3. Administration of baricitinib to patients led to rapid improvement of the disease in all adults and was associated with reduction of systemic inflammation.Conclusions: Patients with this new JAK1 GOF pathogenic variant displayed very high levels of blood histamine and showed a variable combination of atopy with articular and gastrointestinal manifestations as well as calcifying fibrous tumours. The disease, that appears to be linked to STAT3 hyper-activation, was well controlled under treatment by JAK inhibitors in adult patients